Computational study of solvation effects on isomerizations of organic acids and the decomposition of chloroform

Ab initio Monte Carlo simulations have been carried out to study solvation effects on several isomerization reactions and on the reaction mechanism of chloroform decomposition in solutions by means of the combined quantum mechanical and molecular mechanical approach. A free energy perturbation method in the framework of combined quantum mechanical and molecular mechanical potential, called QM/MM-FEP, was designed and was used to calculate the free energy differences of isomers of several organic acids having multiple titration sites, including glycine, 4-methylimidazile, and p-hydroxybenzoic acid. The relative stabilities and acidities/basicities of the isomers were obtained from the QM/MM-FEP simulations. The differences of the solvation free energies were calculated from the gas phase and the solution calculations. Comparisons and analyses of the radial distributions, the solvent coordination numbers, the solvation energies and their components, the solute-solvent energy pair distributions, and the charge distributions were conducted to further understand the solvation effects. The calculations of the isomerization reactions illustrate the importance of the electrostatic interactions in stabilizing the solutes in polar solvents. The decomposition of chloroform was investigated by umbrella sampling. The decomposition mechanism consists of a sequence of reaction steps, including the rate-limiting removal of the first chlorine atom through an SN2 reaction accompanied by a proton transfer reaction, and two subsequent dehalogenation reactions with a concerted and a semi-concerted mechanism, respectively. Computational results were found to be consistent with the experimental data. The study on the degradation of chloroform helps to understand its long lifetime in water.